Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)

• Status: Not yet recruiting
• Trial end date: 2028-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multicenter, interventional, non-randomized study among patients with a relapsed or refractory Wilms tumor. The study will aim to assess efficacy of metronomic chemotherapy, in terms of disease control after two cycles of metronomic chemotherapy.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Oscar Lambret
• Treatments: Etoposide; Irinotecan; Isotretinoin; Temozolomide; Tretinoin; Vincristine

Criteria

Inclusion Criteria:

• Patient ≥18 months old and ≤ 35 years old

• Relapsed or refractory Wilms tumor, histologically proven at diagnosis

• After at least 2 lines of chemotherapy (conventional or high dose, which may include the study molecules) or after 1 line for high risk relapse for which there would not be any curative therapy. If 1 line for high risk relapse, the enrolment should be confirmed by coordinators.

• Radiologically measurable or evaluable disease (visible, target or non-target-lesion on MRI or CT-scan)

• Performance status: Karnofsky performance status (for patients >16 years of age) or Lansky Play score (for patients ≤16 years of age) ≥ 70%.

• Able to take oral medication or nasal gastric tube or authorized gastrostomy

• Adequate biological criteria:

• Neutrophils > 1000/mm3 ; Platelets > 75 000/mm3

• Transaminases (ALT/ AST) ≤ 3 times ULN (or ≤ 6 times ULN if liver metastasis); total bilirubin ≤ 2 ULN (except in case of Gilbert's disease)

• Creatinine ≤ 1,5 ULN or clearance ≥ 60 mL/ min/ 1,73m2 (In case of doubt, to be confirm by assessment of cystatin )

• Females of childbearing potential must have a negative seric pregnancy test within 7 days prior to initiation of treatment.

• Sexually active patients must agree to use adequate and appropriate contraception (at least one highly effective contraception or two complementary methods of contraception), 1 month before beginning of treatment while on study drug and for 6 months after stopping the study drug for both female and male patients.

• Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures according to national guidelines.

• Patient covered by the French "Social Security" regime

Exclusion Criteria:

• Prior history of other cancer within 5 years

• Chemotherapy or radiotherapy of target lesion within 3 weeks prior to inclusion

• Target therapy within less than 5 * half-life of the substance prior to inclusion

• Major surgery within 15 days prior to inclusion

• Presence of any NCI-CTCAE v5 grade ≥ 2 cardiac, hepatic, pulmonary or renal toxicity

• Severe myelosuppression

• Severe peripheral neuropathy (grade ≥ 2)

• Fructose intolerance

• Inflammatory bowel chronic disease and/or intestinal obstruction

• Patients with demyelinating form of Charcot-Marie-Tooth disease

• Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.

• Known hypersensitivity to dacarbazine (DTIC), isotretinoin or to any of the study drugs, study drug classes, excipients in the formulation

• Hyperlipidemia and hypervitaminosis A

• Vaccination with a live attenuated vaccine within 1 month prior to inclusion

• Pregnant or breastfeeding patients

• Inability to comply with medical follow-up of the trial (geographical, social or psychological reasons)